SYMPTOMS OF POST-TRAUMATIC STRESS DISORDER IN INDIVIDUALS WITH MODERATE-TO-SEVERE METHAMPHETAMINE USE DISORDER AND CHANGES WITH TIRZEPATIDE TREATMENT

Background

Post-traumatic stress disorder (PTSD) is prevalent among individuals with methamphetamine use disorder (MtUD) and contributes substantially to psychiatric morbidity and functional impairment. While tirzepatide was being investigated as a potential treatment for methamphetamine use in this study, its impact on co-occurring PTSD symptoms remains unexamined. This research assessed longitudinal changes in PTSD symptoms among participants with baseline provisional PTSD who received tirzepatide.

Methods

Data were obtained from the TRIUMPH (Tirzepatide for Individuals with Comorbid Obesity and Methamphetamine Use Disorder) study, a clinical trial evaluating the efficacy of tirzepatide in adults with moderate or severe MUD (NCT06745128). Provisional PTSD was determined using the PTSD Checklist for DSM-5 (PCL-5) symptom cluster criteria. PTSD symptoms were evaluated longitudinally with the PCL-5, utilizing baseline scores as the reference point in linear mixed-effects models. Baseline demographic and clinical characteristics, including Generalized Anxiety Disorder 7-item (GAD-7), 16-item Quick Inventory of Depressive Symptomatology Self-Report version (QIDS-SR), and irritability domain of Concise Associated Symptom Tracking (CAST-IRR), were summarized for participants who met provisional PTSD criteria. Individuals with moderate-to-severe MtUD who participated in an open-label trial of 32-week-long treatment with tirzepatide for a weight-related indication were included. Self-report symptoms of depression were assessed with the 16-item Quick Inventory of Depressive Symptomatology Self-Report version (QIDS-SR) at baseline (i.e., prior to first injection) and weekly thereafter during the 32-week treatment period and 4-week follow-up period. Repeated-measures mixed-model analyses were used to assess changes in PCL-5 domains.

Results

Twelve participants (out of 35 enrolled) met provisional PTSD criteria at baseline, comprising a subgroup with clinical severity characterized by near-daily methamphetamine use, heightened craving, and considerable psychiatric comorbidity. The mean baseline PCL-5 score was 56.1, and the standard deviation (SD) was 14.72, indicative of severe PTSD symptom burden. Participants also exhibited elevated levels of anxiety (mean GAD-7 = 15.3; SD = 6.11), depression (mean QIDS-SR = 11.0; SD =4.20), irritability (mean CAST-IRR = 20.4; SD =3.65), and functional impairment as compared to those who did not meet the provisional PTSD criteria. Longitudinal analyses demonstrated significant reductions in PTSD symptoms relative to baseline (visit 1) at follow-up visits, with the greatest reduction observed at week-36 (estimate = -20.59, standard error = 7.54; p = .008). Other follow-up visits showed consistent, but nonsignificant, decreases in PCL-5 scores.

Conclusions

In adults with methamphetamine use disorder meeting provisional PTSD criteria, tirzepatide administration was associated with clinically meaningful reductions in PTSD symptom severity over time. These findings underscore the importance of evaluating comorbid psychiatric symptoms in substance use intervention trials and further investigation in larger studies.